(Wrong) lessons learned
The main way we approach an outbreak today is to gather the maximum amount of data available to suggest pathways of containment. Although effects of an epidemic are felt throughout all sectors from tourism to education all the way to the job market, proactive initiatives are typically assigned to only two key fields: research and public health (6,7). Consistent throughout the majority of the reports and studies is the general aim of increasing preparedness measures (7,8), which translates into two major suggested outputs:
Rapid response: the main direction for developments in public health is improving preparedness. This involves decreasing the time required to identify and respond to an emerging disease. Identification of a public health event of international concern (PHEIC) requires investment into outbreak surveillance, healthcare data management, reaction protocols and real-time communication channels between local health authorities and regional or global organisations (7,9). Response on the other hand warrants sufficient capacity in healthcare infrastructure to treat incoming waves of patients, and therefore relies on stockpiling equipment and medication and increasing the number of trained healthcare professionals (6,10).
Focused research: the main directions for developments in science is increasing our knowledge on the emerging disease. A typical reaction to an epidemiological emergency is the reallocation of research funds towards studies targeting the emergent pathogen, which shifts the focus of novel and existing labs. Unfortunately, analyses show that this heightened attention and support wanes with the decreasing sense of emergency and proves to be inefficient in the long term, thus often referred to as ‘boom-and-bust’ funding (11,12).
Both outputs have had significant results in managing re-emergence of known diseases and managing epidemics that are considered regular occurrences in particular regions, but neither has yielded any considerable advantages against the EID crisis (9,13). The reason is that all of the initiatives listed above require the prior knowledge of the emergent pathogen. Public health needs to ‘know what they’re looking for’ to detect it and alert health systems at an early stage of the outbreak. Otherwise the only clue of a recent emergence is the sudden spike of patients producing similar symptoms with unknown aetiology, as was the case for SARS-CoV-2 (14) the 2015 Zika epidemic (15), or even the currently ongoing outbreaks of hepatitis among children (16). Response also requires data on the clinical manifestations, morbidity and mortality to adequately prepare healthcare infrastructures, and focusing research requires an already identified and defined target pathogen or disease. In case of a newly emerging disease, none of the above described information is available, crisis response is therefore constantly lagging behind the spread of the epidemic. Taking into consideration the effects of globalised travel and trade (13,17), preparatory efforts will have little success in halting an epidemic in fulfilling its pandemic potentials, and crisis response is, by definition, a reactive measure.
To successfully address the emergence of novel diseases, a new paradigm has to be introduced into global health security, shifting our main focus from preparedness over to prevention, and moving our intervention further up the infection timeline. However, in order to change our approach, we must understand the gaps that have thus far allowed EIDs to ravage our societies.
What are we missing?
Health security measures are developed by close collaboration networks between public health and fundamental science. With the constant advancements in both technology and research, numerous defence strategies have been improved. Nevertheless, the EID crisis represents a completely novel challenge, which requires understanding the limitations of our current approaches, particularly about the predictability and the scope of EIDs.
Predictability
Despite the extent to which epidemics and pandemics damage a wide range of socio-economic landscapes, there are a concerningly few initiatives aiming to prevent large scale effects of EIDs (18,19). This is due to the prevailing evolutionary paradigm used in public health and research regarding the ability of pathogens’ to colonise new hosts a.k.a. emerge as a novel disease. The traditional scientific paradigm states that there is strong selection acting on parasite characteristics, which leads to extreme specialisation to a narrow range, often a single host species. Such specialised parasites are able to better exploit host resources, but at the same time lose their ability to infect novel host organisms, therefore any novel colonisation must necessarily be preceded with the right mutation appearing at the right time (20). Due to the random and unpredictable nature of such genetic changes, host switching events are assumed to be rare and unpredictable (1,21). However, this co-evolutionary theory suffers from severe shortcomings, when compared to empirical data: (I) its key assumption of parasites being tightly co-adapted to a narrow range of hosts lack empirical support, (II) its prediction regarding EIDs being rare occurrences is sharply contradicted by the accelerating EID crisis (22–24) and (III) it fails to connect such novel colonizations events to environmental changes when there is evidence that emergences cluster around climate change perturbations (25,26).
This contradiction between the prevailing paradigm and empirical observations is referred to as the Parasite Paradox (27), with a significant consequence on how public health addresses EIDs: it deems emergence rare, and therefore of low global health concern, and at the same time unpredictable, thus deeming prevention efforts impossible. These wrong predictions are the main reasons public efforts aiming to address the EID crisis have been futile, and precisely why we need a novel evolutionary paradigm to resolve this paradox.
The Stockholm Paradigm
The Stockholm Paradigm (SP) (1,26,28) relies on two Darwinian principles leading to fundamentally different conclusions than the co-evolutionary theory.
First, evolutionary outcomes are always local. Pathogens are genetically capable of infecting a certain range of hosts, translated as their ‘fundamental fitness space’, but only infect a subset of these that are available to them in their environment, creating their ‘realised fitness space’. Selection only acts on traits within the realised fitness space and has no effect on other, potential hosts in other environments. Pathogens with proportionally smaller realised fitness space therefore have a higher potential of colonising a novel host, without the necessity of evolving new capacities. This potential is referred to as ecological fitting (29). When viewed from a public health perspective, this means emergence is a built in attribute of host-pathogen associations and is therefore expected to happen frequently, especially when environmental perturbations increase species encounters, which is what we are witnessing with the EID crisis.
Second, evolution is conservative. In order to utilise particular resources, pathogens will develop specialised traits. Since these traits are phylogenetically conservative, pathogens will be able to utilise distantly-related, naive host species upon encounter, while the same host can serve as a resource for various pathogens (30–32). The recently emerged SARS-COV-2 uses the angiotensin I converting enzyme 2 (ACE2) as its main receptor, which is widely shared among distant groups of mammals, and is the primary reason why the pathogen had established itself in mustelids, felines and cervids, among other mammals (33,34) Translated to a practical view, conservative traits allow us to predict the risk an unknown pathogen poses to human populations without having to wait for an outbreak. Pathogenic microbes can therefore be sampled from reservoir species and action can be taken not only to contain emergence, but to prevent it all together.
The SP therefore changes the theoretical foundation on which our global health security infrastructure is built. The bad news is that EIDs are indeed frequent and should only be expected to increase in occurrence with the intensifying globalisation and climate change. The good news, however, is that EIDs are predictable, and preventive action can and should be taken to avoid the next epidemic and pandemic.
Scope
When referring to EIDs, literature and policy refers to almost exclusively human pathogens (13,17,35). Preparatory efforts and early action plans exclusively target human diseases, which manifests in recommended actions for Rapid Response and Focused Research(36,37). However, this also narrows our view to a small subset of potentially dangerous pathogens, while we ignore those affecting crops and livestock. Infectious diseases decimating agricultural production are dealt with by food security, agri-food sciences and agricultural policies, and are barely put in the context of EIDs . Nevertheless, the loss of production and associated costs affect regions’ economies just as much, if not more than human diseases do. Coconut Lethal Yellowing Disease destroyed 95% of coconut palms in a region of Mexico, killed millions of trees in Nigeria affecting the livelihood of 30000 families, and ruined 72-99% of trees in West Africa (38,39). Wheat stem rust (Puccinia graminis f. sp. ) was considered eradicated until 1998, when a new, highly virulent strain emerged in Uganda (40). Since then, it has spread throughout Eastern and South Africa, the Middle East and Western Europe, and poses a threat to over 80% of the world’s wheat varieties (41). From those affecting livestock, the 2014-15 avian influenza epidemic led to the culling of 45 million birds in the US, and export bans in 75 countries (42)ongoing H5N1 avian influenza outbreak already led to the loss of 77 million birds (43). Within a few years, African Swine fever (ASF) swept through Europe and Asia, destroying 20% of Vietnam’s swine population and resulting in 141 billion USD economic loss for China, collapsing half the world’s pork export market in a single year (44). Apart from the obvious socio-economic effects of food shortage and skyrocketing food prices, policy interventions aimed at relieving damages of ASF were suggested to have led to the emergence of COVID (45).
Although currently considered as separate issues of human wellbeing, food security and global health security are threatened by the same thing: Emerging Infectious Diseases. If we understand the dynamic allowing novel pathogens to explore and colonise new hosts, then we must also understand that this applies to not only humans invading natural habitats, but to our crops and livestock being placed in the close vicinity of natural reservoirs (46,47).
With EIDs being predictable, but much more frequent and abundant than previously thought, health security measures have to incorporate this new paradigm and adopt appropriate and much called for prevention measures (48). We therefore describe a comprehensive four-step protocol based on the SP and leading all the way to policy implementations.
The DAMA Protocol
The DAMA - Document, Assess, Monitor, Act - is a policy plan derived directly from the evolutionary framework of the Stockholm Paradigm, which aims to connect evolutionary science with applied health security. It focuses on preventing outbreaks and facilitating communication between private and public actors, knowledge institutions and communities directly affected (Fig 1, redrawn and modified from (21).
Documenting pathogens has to be extended from only those already causing diseases to those documented in wild animal and plant populations. Taking advantage of the evolutionary context provided by the SP, anticipatory research has to focus on potential reservoirs. Pathogens causing disease in humans, crops or livestock are all present in at least one other species that manifests no symptoms. Taxonomic inventories, virological and bacteriological studies have often revealed these pathogen-reservoir associations, which direct research focus on a subset of species within any given area. Pathogen transmission occurs on the interface between such reservoirs and human settlements, agricultural areas and breeding facilities (49–51). The primary step in establishing a preventive protocol is collecting all information into strategic inventories feeding into archives of host and pathogen specimens, modes of transmission and potential vectors (52,53). Finally, inventories are also to include local and traditional knowledge on the distribution, behaviour and abundance of reservoirs, which calls for the establishment of robust science-society collaborative programs (1,54,55).
Inventories then allow us to Assess the risk posed by potential pathogens. A three step process first separates our potential pathogens, from those already known and those considered to non-pathogenic through phylogenetic triage , then usesphylogenetic assessment to determine mode of transmission, reservoirs and potential vectors, and finally maps population genetics and rare genotypes through population modelling .
Potential pathogens are then Monitored to create a detailed distribution map in areas already confirmed as well as those deemed suitable. Changes in geographic distribution, host range, mode of transmission or disease pathology are early signs of potential emergence on interfaces between populations of reservoirs and susceptible hosts (47).
Adequate monitoring sets the stage for adequate Action in policy-making. Highly dependent on the context such as legal environment, policy modifications concern areas such as food safety, wildlife management, veterinary medicine, public health and education. Due to the high number of stakeholders affected by EID outbreaks, preventive action has to be designed by multi-actor task forces representing expertise from various sectors and scales. In practice, this necessitates the collaborative work of scientists, private and government practitioners, policy-makers and local experts. This collaboration can be realised by employing transdisciplinary approaches. The latter can be defined as “a critical and self-reflexive research approach that relates societal with scientific problems‘ … [and] produces new knowledge by integrating different scientific and extra-scientific insights” (56) and are increasingly recognised for their potential to tackle complex real-life issues by integrating different kinds of knowledge (57,58).
Contrary to pandemics and large epidemics, emergence always takes place on a small, local scale, which calls for the facilitation of bottom-up effects and the subsequent co-accommodation of grassroots and institutional settings. When establishing task forces putting science into action, initiators have to consider implementation strategies on various scales (global, regional, local) and policy environments (human, livestock and crop health security).
Implementation strategies on different scales
Global
Current global frameworks are all based on managing existing diseases and increasing palliation and preparedness for those newly emerging (59,60). Since they are all based on the assumption that EIDs are rare and unpredictable, plans to prevent outbreaks are slim to none. Nevertheless, most of the global frameworks in use name prevention of disease as their main aim, which refers to containing diseases on the level of outbreak, halting large scale transmission and thus avoiding outbreaks from growing into epidemics. Although we can understand restricting pathogens from spreading beyond small, local outbreaks as preventing epidemics, we argue that prevention should be used in the context of avoiding emergence in the first place. This shift in epistemics is also strongly supported by the grave predictions regarding the speed with which smaller outbreaks can spread out in an increasingly globalised world (17,61,62), narrowing the time window available for containment measures.
One the one hand, global health security has to adopt a novel evolutionary paradigm to adjust risks and predictions regarding EIDs. On the other hand, the epistemology and definition of prevention needs to be unified across all global guidelines to focus efforts in both containing and preventing diseases in an evolutionary context. Therefore, current measures have to be evaluated to determine their applicability and limitations, and prevention has to be contextualised within global health security.
The Prevent - Prepare - Palliate (3P) framework offers a comprehensive, systemic characterization of existing health security initiatives and describes how prevention can be adopted into current infrastructures (21). Implementing prevention into global healthcare frameworks will help identify gaps that allow EIDs to emerge at an accelerating rate and would provide guidelines for healthcare infrastructures to intervene on a regional level.
Regional
Managing diseases on a regional level faces the challenge of having to act in various different policy and cultural environments. Ranging from upper regional levels such as international alliances (e.g. European Union) operating within large scale legal environments such as EU regulations through mid-regional levels concerning one or a few neighbouring countries to lower regional levels involving small municipalities managing local communities, regional scales are the most diverse in terms of expertise, jurisdiction and policies. Nevertheless, epidemics of national concern are dealt with on regional levels, involving municipalities directly affected as well as national health care infrastructures and public health institutions (9). Therefore, implementing the DAMA protocol on a regional scale requires carefully selected methods facilitating intersectoral collaboration and defining outcomes accommodating local policy environments.
Living Labs
From the toolkits of transdisciplinary methods, Living Labs (LLs) provide an opportunity to establish solid, well thought out task forces bringing the skills and capacities of different actors required for addressing a particular issue together (63). Living Labs can be defined as both “an arena (i.e., geographically or institutionally bounded spaces) and … an approach for intentional collaborative experimentation of researchers, citizens, companies and local governments” (64). It makes them suitable for dealing with healthcare issues, as they are designed to foster intersectoral communication and collaboration, and thus increase the feasibility of intervention plans by fitting them to local policy environments and interests of affected stakeholders (65). If designed and implemented well, the LL approach can also help avoid stumbling blocks (e.g. disciplinary boundaries and silos between science, practice and society, low feasibility in diverse policy environments, low level of adaptability to local cultural, societal, environmental settings, decreasing trust in policy and politics, etc.) by involving diverse experts on legal limitations, local settings and market conditions, and finally foster knowledge exchange and widen professional networks.
Containing outbreaks or epidemics requires a joint collaboration between private and public sectors, as well as science and society, and prevention is no different. Current solutions are mostly characterised by hasty and temporary collaborations formed under the pressure of a health emergency. Living Labs are potentially a very impactful approach for dealing with EID crises. They have been proliferating in Europe since 2006, when the European Network of Living Labs (ENoLL) was founded as a platform for best practice exchange, and have since been successfully adopted in domains such as food bioeconomy, agriculture, environmental, urban and rural development (64,66,67). However, to date Living Labs have hardly ever been applied to the area of EIDs. Apart from the benefits of the LL approach discussed above more generally, LLs can also enable and foster discussion between authorities, science and the public thereby addressing the dire consequences of public distrust in science and science-based policies revealed by the COVID-19 pandemic has revealed the dire consequences of public distrust in science and science-based policies (68,69).
Given the various actors impacted by infectious disease outbreaks, LL setups are able to generate solutions across disciplines, making them a ‘proliferating approach to working in a transdisciplinary fashion’ (57). Stakeholders are selected based on their expertise and involvement in the context of EIDs, making them highly adaptable and specific to the issue investigated. Selection must also consider the highest-level decision-makers needed for efficient intervention (municipality governance and policy-makers, national government officials, regional public health authorities, etc.) Participants generally represent four larger sectors (Figure 1.).
  1. Public actors - policy- and decision-makers, legal experts and government officials; expertise in the legal environment and regulatory role in the long-term management of the outcome. Typical actors for disease management are Public Health Authorities, Municipality Governance or Food Safety Control.
  2. Private actors - private institutions, organisations and companies affected by the emergence; insights into practical and industrial implementability of intervention plans. Managing disease will be of interest to agricultural organisations and farmers’ associations, livestock breeders and food production companies, travel agencies or pharmaceutical companies.
  3. Knowledge institutions - scientific expertise on the emerging pathogen generate predictions related to transmission, epidemic and pandemic potential and risk assessment. Partners to consider in relation to EID are university research groups, independent research institutions and scientific organisations (e.g. Chatham House, Milken Institute).
  4. Local citizens - it is crucial to include members of the community directly affected by potential emergence. In addition to increasing feasibility of the intervention plans among local conditions, involvement raises awareness of healthcare threats and provides the community with a sense of ownership over the situation. An emphasis must be placed on reaching out to local Citizen Science Programs who have extensive experience in not only local settings, but research processes.